WO1988005774A1 - Derives de l'acide (r) 5-pentylamino-5-oxopentanoique a activite anticholecystoquinine - Google Patents
Derives de l'acide (r) 5-pentylamino-5-oxopentanoique a activite anticholecystoquinine Download PDFInfo
- Publication number
- WO1988005774A1 WO1988005774A1 PCT/EP1988/000061 EP8800061W WO8805774A1 WO 1988005774 A1 WO1988005774 A1 WO 1988005774A1 EP 8800061 W EP8800061 W EP 8800061W WO 8805774 A1 WO8805774 A1 WO 8805774A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- formula
- compounds
- pentylamino
- derivatives
- group
- Prior art date
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/08—Antiepileptics; Anticonvulsants
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/02—Preparation of carboxylic acid amides from carboxylic acids or from esters, anhydrides, or halides thereof by reaction with ammonia or amines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C233/12—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by halogen atoms or by nitro or nitroso groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/64—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings
- C07C233/81—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups
- C07C233/82—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom
- C07C233/83—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom of an acyclic saturated carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
Definitions
- the subjects of the present invention are original derivatives of (R) 5-pentylamino-5-oxopentanoic acid, which may be represented by the general formula indicated below:
- R 1 is selected from the groups 2-naphthyl, 3,4-dichlorobenzoyl and 3,4-dimethyl-benzoyl and R 2 is a pentyl group or an alkoxyalky group with 4 carbon atoms, and in which the substituents on the central chiral group (marked with an aserisk in Formula (I)) have the R (rectus) conformation.
- R 2 is preferably selected from the group consisting of the pentyl, 2-ethoxyethyl and 3-methoxypropyl groups.
- the compounds which are the subject of the present invention display a powerful antagonistic activity towards cholecystokinin (CCK).
- CCK cholecystokinin
- the compounds according to the invention may thus be used to advantage in the treatment of various illnesses in man, such as illnesses of the digestive system, as for example, in the treatment of colitis, of biliary diskinesia and pancreatitis.
- their use may also be envisaged in the treatment of mental disorders attributable to deficiencies in the physiological neuron levels of CCK or of other related bioactive polypeptides and also in the treatment of anorexia.
- these compounds are also very active in vivo.
- pancreatitis induced by sodium taurocholate.
- compositions which are the subject of the invention may be prepared by conventional techniques, for example as pills, capsules, suspensions, solutions and suppositories and may be administered orally, parenterally or rectally.
- the active ingredient is administered to the patient typically in a ratio of 0.005 to 5 mg/kg of body weight per dose.
- a water-soluble salt of the subj ect compounds such as the sodium salt or another salt which is non-toxic and pharmaceutically acceptable.
- Substances commonly used in the pharmaceutical industry as excipients, binders, flavourings, dispersants, colouring agents, humectants, etc. may be used as inactive ingredients.
- the present invention arises from the following two considerations:
- the method for the preparation of the derivatives which are the subject of the present invention is characterised in that it comprises the steps of: a) reacting the gamma-benzyl ester of N-carbobenzoxy-D-glutamic acid with an amine of formula , in which R 2 has the meaning attributed to it above, by the mixed anhydride method in an inert anhydrous solvent at a temperature of between -15 ° and +15 ° to give the compounds of formula
- the amidation step (a) is carried out preferably at a temperature of between -15 ° and -10 o C over a period of from 1 to 24 hours, preferably for 6 hours with the reagents in a stoichiometric ratio.
- the preferred solvent for the reaction is selected from chloroform, dioxan and tetrahydrofuran.
- the hydrogenation step (b) is preferably carried out in the presence of palladium supported on carbon, with between 0.02 and 0.001 atoms of palladium per mole of compound (III), in a methanolic solution, at ambient temperature and pressure, in a stream of hydrogen for a period of from 1 to 12 hours, preferably 3 hours.
- the acylation step (c) is preferably carried out at a temperature of approximately 5 o C for a period of from 1 to 24 hours, preferably 12 hours.
- the temperature is maintained at -10 o C for 20 minutes and then 15.7 g (0.1 moles) of di-pentylamine are added. Agitation is continued for a further 6 hours and the temperature rises to ambient temperature; it is dried and the residue is taken up in ethyl acetate.
- TLC Rf 0.75 (n-Butanol-acetic acid-H 2 O 5/2/2 V/V/V).
- the mixture is left for 12 hours to react.
- Table 4 shows some of the (S) 4-acylamino-5-(di-n- pentylamino)-5-oxopentanoic derivatives thus obtained and used for the pharmacological comparisons with some of their identifying characteristics.
- the ox gallbladder cell membranes were homogenised with Tris buffer (pH 7.4) and the homogenate was centrifuged at 50,000 gravity for 10 minutes. The membranes were then incubated with a radioactive tracer and the compounds under study for 2 h at 25°C.
- the radioactivity associated with the pellet was determined with a liquid scintillator.
- the specific binding was determined as the difference between the binding in the absence and in the presence of 10 -6 M CCK-8.
- the emptying of the gallbladder was induced by a single oral administration of 1 ml of a 30% suspension (weight/volume) of lyophilised egg yolk in a physiological solution.
- the egg yolk induces the release of endogenous CCK. This dose was selected as it causes practically complete emptying of the gallbladder.
- the antagonist compounds were administered intraperitoneally (i.p.) 15 minutes before the contractant.
- the % antispastic activity for each dose was calculated by the following formula:
- P 1 average weight of the gallbladders of the group of animals treated with the drug plus the contractant
- P 2 average weight of the gallbladders of the group of animals treated with contractant only
- P 3 average weight of the gallbladders of the control group of animals.
- the compounds were tested in various doses so as to enable the calculation of the ID50 value, that is the dose (in mg/kg i.p.) which is able to inhibit the contractant effect of the egg yolk by 50%.
- PAPAVERINE 25 0 50 0 INACTIVE 75 26.1 (1) r the coefficient of correlation of the straight line of regression.
- Compound 7 at a dose of 0.1 mg/kg, blocks the contraction induced by the egg yolk by approximately 75%.
- Its (S) enantiomer is also active but with an ID50 value approximately 60 times larger.
- Atropine on the other hand is inactive and papeverine is slightly active, but only at the toxic dose of 75 mg/kg, which causes the death of 20% of the animals treated.
- This experiment shows the contractant effect of CCK on the piloric sphincter.
- a dose of 8mcg/kg i.p. of CCK was used, which induces a sub-maximal contraction of the pilorus.
- the antagonistic compounds were administered (i.p.) 15 minutes before the contractant. 10 minutes after the administration of the contractant, the animals were treated per os with 25 ml/kg of H 2 O. 5 minutes after this administration, the animals were killed, their stomachs removed and the gastric content measured by removal with a syringe.
- the % antispactic activity for each dose administered was calculated from the following formula:
- V 1 the gastric-content volume of the group of animals treated with the drug plus the contractant
- V 2 the gastric-content volume of the group of animals treated with the contractant only
- V 3 the gastric-content volume of the control group of animals.
- the compounds were tested at various doses so as to enable the calculation of the ID50 value, that is the dose (in mg/kg i.p.) which is able to inhibit the contractant effect of CCK by 50%.
- the piloric contraction caused by 8mcg/kg of CCK-8 is inhibited by 50% by some of the compounds of the invention at very low doses, 30 mcg/kg in the case of compound 7, that is at a dose only 3-4 times greater than that of the hormonal contractant.
- Compound 13, on the other hand, which is the S enantiomer of compound 7, is active only at doses approximately 150 times higher.
- the products under test were administered intraperitoneally (i.p.) 30 minutes before the operation and 3 hours after the operation. 6 hours after the laparotomy and after anaesthesia with ether, blood was removed from the retro-orbital plexus, the animals were killed and the pancreas removed and weighed. The activity of the serum amylase was determined by the Ceska method (Clin. Chim. Acta 26 (1969), 437-444).
- the compounds were tested at different doses so as to enable the calculation of the ID50 value, that is the dose (in mg/kg i.p.) which is able to inhibit the toxic effect of the sodium taurocholate by 50%, expressed both as a % inhibition of the increase in weight of the pancreas and as a % inhibition of the increase in serum amylase.
- the results obtained with compounds 7 and 8 are given in Table 8.
- Table 8 Examples of proteolytic activity of the claimed compounds in experimental pancreatitis induced by taurocholate in rats
- the serum amylase almost doubles.
- a dose of approximately 0.5 mg/kg i.p. of the compound 7 inhibits the increase in weight of the pancreas and the increase in serum amylase by 50%.
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Epidemiology (AREA)
- Pain & Pain Management (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Fats And Perfumes (AREA)
- Cephalosporin Compounds (AREA)
Abstract
Dérivés optiquement actifs de l'acide (R) 5-pentylamino-5-oxopentanoïque et leurs sels pharmaceutiquement acceptables qui ont une action antagoniste sur la cholecystoquinine, de formule (I), dans laquelle R1 est choisi dans les groupes 2-naphtyle, 3,4-dichlorobenzoyle et 3,4-diméthylbenzoyle et R2 est un groupe pentyle ou un groupe alkoxyalkyle à 4 atomes de carbone et dans laquelle les substituants dans le groupe chiral central (affecté d'un astérisque dans la formule (I)), ont la conformation R (rectus).
Priority Applications (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE88901259T DE3885889T2 (de) | 1987-02-05 | 1988-01-28 | (r)5-pentylamino-5-oxopentanesäure-derivate mit anticholecystokininwirkung. |
AT88901259T ATE97653T1 (de) | 1987-02-05 | 1988-01-28 | (r)5-pentylamino-5-oxopentanesaeure-derivate mit anticholecystokininwirkung. |
DK554688A DK172007B1 (da) | 1987-02-05 | 1988-10-04 | Farmaceutisk aktive derivater af (R)-5-pentyl-amino-5-oxopentansyre og farmaceutisk præparater deraf |
KR1019890701722A KR950006573B1 (ko) | 1988-01-21 | 1989-01-20 | 유리 빌딩 블럭을 구비한 벽의 조립을 위한 프레임 구조물 |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
IT8767076A IT1217123B (it) | 1987-02-05 | 1987-02-05 | Derivati otticamente attivi dell acido 5 pentilammino 5 oxo pentanoico r ad attivita antagonista della colecistochinina e procedimento per la loro preparazione |
IT67076A/87 | 1987-02-05 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1988005774A1 true WO1988005774A1 (fr) | 1988-08-11 |
Family
ID=11299376
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/EP1988/000061 WO1988005774A1 (fr) | 1987-02-05 | 1988-01-28 | Derives de l'acide (r) 5-pentylamino-5-oxopentanoique a activite anticholecystoquinine |
Country Status (12)
Country | Link |
---|---|
US (3) | US5130474A (fr) |
EP (2) | EP0344184B1 (fr) |
JP (1) | JPH075534B2 (fr) |
AT (1) | ATE131153T1 (fr) |
AU (1) | AU606390B2 (fr) |
CA (1) | CA1339917C (fr) |
DE (2) | DE3854764T2 (fr) |
IE (1) | IE63369B1 (fr) |
IT (1) | IT1217123B (fr) |
PT (1) | PT86700B (fr) |
WO (1) | WO1988005774A1 (fr) |
ZA (1) | ZA88733B (fr) |
Cited By (22)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4971978A (en) * | 1987-09-21 | 1990-11-20 | Nadzan Alex M | Derivatives of D-glutamic acid and D-aspartic acid |
GR900100516A (en) * | 1989-07-07 | 1991-12-10 | Abbott Lab | Cck analogous amino-acid antagonists |
WO1993014066A1 (fr) * | 1992-01-09 | 1993-07-22 | James Black Foundation Limited | Derives d'acides amines avec une activite anticholecystokinine |
US5716958A (en) * | 1994-10-27 | 1998-02-10 | Tobishi Pharmaceutical Co., Ltd. | Amino acid derivative having anti-CCK activity |
EP2088154A1 (fr) | 2004-03-09 | 2009-08-12 | Ironwood Pharmaceuticals, Inc. | Procédés et compositions pour le traitement de troubles gastro-intestinaux |
WO2010065751A2 (fr) | 2008-12-03 | 2010-06-10 | Synergy Pharmaceuticals, Inc. | Formulations d'agonistes de guanylate cyclase c et méthode d'utilisation |
EP2246360A1 (fr) | 2003-01-28 | 2010-11-03 | Ironwood Pharmaceuticals, Inc. | Compositions pour le traitement de troubles gastrointestinaux |
WO2011069038A2 (fr) | 2009-12-03 | 2011-06-09 | Synergy Pharmaceuticals, Inc. | Agonistes de la guanylate cyclase utiles dans le traitement de l'hypercholestérolémie, de l'athérosclérose, d'une coronaropathie, des calculs biliaires, de l'obésité et d'autres maladies cardiovasculaires |
WO2012118972A2 (fr) | 2011-03-01 | 2012-09-07 | Synegy Pharmaceuticals Inc. | Procédé de préparation d'agonistes du guanylate cyclase c |
WO2013138352A1 (fr) | 2012-03-15 | 2013-09-19 | Synergy Pharmaceuticals Inc. | Formulations d'agonistes de la guanylate cyclase c et procédés d'utilisation |
WO2014029983A1 (fr) | 2012-08-21 | 2014-02-27 | Ardelyx, Inc. | Composés et procédés d'inhibition d'un antiport à médiation par nhe dans le traitement de troubles associés à une rétention de fluide ou à une surcharge de sel et de troubles du tractus gastro-intestinal |
WO2014151206A1 (fr) | 2013-03-15 | 2014-09-25 | Synergy Pharmaceuticals Inc. | Agonistes de la guanylate cyclase et leurs utilisations |
WO2014151200A2 (fr) | 2013-03-15 | 2014-09-25 | Synergy Pharmaceuticals Inc. | Compositions utiles pour le traitement de troubles gastro-intestinaux |
EP2810951A2 (fr) | 2008-06-04 | 2014-12-10 | Synergy Pharmaceuticals Inc. | Agonistes de guanylate cyclase utile dans le traitement de troubles gastro-intestinaux, d'une inflammation, d'un cancer et d'autres troubles |
WO2014197720A2 (fr) | 2013-06-05 | 2014-12-11 | Synergy Pharmaceuticals, Inc. | Agonistes ultra-purs de guanylate cyclase c, leur procédé de production et d'utilisation |
EP2998314A1 (fr) | 2007-06-04 | 2016-03-23 | Synergy Pharmaceuticals Inc. | Agonistes de guanylase cyclase utiles pour le traitement de troubles gastro-intestinaux, d'inflammation, de cancer et d'autres troubles |
EP3241839A1 (fr) | 2008-07-16 | 2017-11-08 | Synergy Pharmaceuticals Inc. | Agonistes de guanylate cyclase utiles pour le traitement de troubles gastro-intestinaux, inflammatoires, cancéreux et autres |
WO2018129557A1 (fr) | 2017-01-09 | 2018-07-12 | Ardelyx, Inc. | Inhibiteurs d'antiport à médiation par nhe |
WO2018129556A1 (fr) | 2017-01-09 | 2018-07-12 | Ardelyx, Inc. | Composés et procédés pour l'inhibition d'un antiport à médiation par échangeur sodium/proton (nhe) dans le traitement de troubles associés à une rétention d'eau ou à une surcharge en sel et de troubles du tractus gastro-intestinal |
WO2018129552A1 (fr) | 2017-01-09 | 2018-07-12 | Ardelyx, Inc. | Composés utiles pour le traitement de troubles du tractus digestif |
EP3351248A1 (fr) | 2008-12-31 | 2018-07-25 | Ardelyx, Inc. | Composés et procédés d'inhibition d'un antiport à médiation par nhe dans le traitement de troubles associés à une rétention de fluide ou à une surcharge de sel et de troubles du tractus gastro-intestinal |
CN108912007A (zh) * | 2018-06-20 | 2018-11-30 | 中国农业科学院兰州畜牧与兽药研究所 | 一种右氯谷胺的制备方法 |
Families Citing this family (18)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4792555A (en) * | 1987-03-20 | 1988-12-20 | American Home Products Corporation | Phospholipase A2 inhibitors |
DE69017302T3 (de) * | 1989-08-04 | 1999-08-05 | Merck Sharp & Dohme Ltd., Hoddesdon, Hertfordshire | Zentrale Cholecystokinin-Antagonisten zur Behandlung von psychiatrischen Krankheiten. |
JP2578044B2 (ja) * | 1992-03-14 | 1997-02-05 | 呉羽化学工業株式会社 | フェニルアラニン−グリシン誘導体、その製造方法、及びその誘導体を含有する抗腫瘍剤 |
US7183485B2 (en) * | 2003-03-11 | 2007-02-27 | Micron Technology, Inc. | Microelectronic component assemblies having lead frames adapted to reduce package bow |
ITTO20030474A1 (it) * | 2003-06-23 | 2004-12-24 | Rotta Res Lab Spa Ora Rottapharm Spa | Procedimento per la preparazione di dexloxiglumide |
US7553873B2 (en) * | 2005-07-11 | 2009-06-30 | Wyeth | Glutamate aggrecanase inhibitors |
US7863330B2 (en) | 2006-06-14 | 2011-01-04 | Rottapharm S.P.A. | Deloxiglumide and proton pump inhibitor combination in the treatment of gastrointestinal disorders |
CL2007002070A1 (es) | 2006-07-14 | 2008-02-08 | Ac Immune S A Genentech Inc | Anticuerpo quimerico o humanizado, o fragmentos de ellos, que se adhieren especificamente a por lo menos un epitopo en la proteina beta-amiloide; molecula de acido nucleico que lo codifica; composicion que lo comprende; su uso para tratar enfermedade |
EP2574345A1 (fr) * | 2007-06-12 | 2013-04-03 | AC Immune S.A. | Anticorps humanisés à amyloïde bêta |
US8613923B2 (en) | 2007-06-12 | 2013-12-24 | Ac Immune S.A. | Monoclonal antibody |
US8048420B2 (en) | 2007-06-12 | 2011-11-01 | Ac Immune S.A. | Monoclonal antibody |
EP2650308A3 (fr) * | 2007-10-05 | 2014-11-12 | Genentech, Inc. | Utilisation d'anticorps anti-beta amyloide aux maladies oculaires |
WO2009048539A2 (fr) * | 2007-10-05 | 2009-04-16 | Genentech, Inc. | Anticorps monoclonal |
NZ606357A (en) | 2010-07-30 | 2015-05-29 | Genentech Inc | Safe and functional humanized anti beta-amyloid antibody |
JP5785045B2 (ja) * | 2011-10-06 | 2015-09-24 | エヌ・イーケムキャット株式会社 | 選択的脱ベンジル化方法およびこれに用いる選択水素化触媒 |
US10376481B2 (en) | 2012-08-21 | 2019-08-13 | Ardelyx, Inc. | Compounds and methods for inhibiting NHE-mediated antiport in the treatment of disorders associated with fluid retention or salt overload and gastrointestinal tract disorders |
CA2909169A1 (fr) | 2013-04-12 | 2014-10-16 | Ardelyx, Inc. | Composes de liaison a nhe3 et procedes d'inhibition du transport de phosphate |
EP3277274B1 (fr) | 2015-04-01 | 2024-06-12 | Cedars-Sinai Medical Center | Analogues ou dérivés de lovastatine anti-méthanogènes et leurs utilisations |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE2049332A1 (de) * | 1969-10-13 | 1971-04-22 | Rotta Research Laboratorium SpA, Mailand (Italien) | Verfahren zur Herstellung von therapeu tisch aktiven Amiden der N Benzoylglutamm saure |
GB2160869A (en) * | 1984-06-25 | 1986-01-02 | Rotta Research Lab | Glutamic and aspartic acid derivatives |
WO1987003869A2 (fr) * | 1985-12-17 | 1987-07-02 | Rotta Research Laboratorium S.P.A | Dervies pharmaceutiquement actifs d'acides glutamiques et aspartiques |
Family Cites Families (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3551417A (en) * | 1967-08-28 | 1970-12-29 | Universal Oil Prod Co | Pesticidal heterocyclic sulfides |
US3587048A (en) * | 1969-10-10 | 1971-06-22 | Itt | Status control system |
LU78804A1 (de) * | 1977-12-30 | 1979-07-20 | Byk Gulden Lomberg Chem Fab | N-substituierte w-aminoalkanoyl-w-aminoalkansaeuren,ihre verwendung und verfahren zu ihrer herstellung sowie diese verbindungen enthaltende arzneimittel |
IT1178982B (it) * | 1984-06-25 | 1987-09-16 | Rotta Research Lab | Derivati del acido gludamico aventi attivita antagonista su polipep tidi bioattivi e procedimento per la loro preparazione |
US4880938A (en) * | 1986-06-16 | 1989-11-14 | Merck & Co., Inc. | Amino acid analogs |
IT1196849B (it) * | 1986-12-16 | 1988-11-25 | Rotta Research Lab | Nuovi derivati degli acidi 5 pentilammino 5 oxo pentaoico e 4 pentilammino 4 oxo butanoico ad attivita antagonista della colecistochinina e procedimento per la loro preparazione |
-
1987
- 1987-02-05 IT IT8767076A patent/IT1217123B/it active
-
1988
- 1988-01-28 DE DE3854764T patent/DE3854764T2/de not_active Expired - Fee Related
- 1988-01-28 EP EP88901259A patent/EP0344184B1/fr not_active Expired - Lifetime
- 1988-01-28 DE DE88901259T patent/DE3885889T2/de not_active Expired - Fee Related
- 1988-01-28 WO PCT/EP1988/000061 patent/WO1988005774A1/fr active IP Right Grant
- 1988-01-28 AU AU12282/88A patent/AU606390B2/en not_active Ceased
- 1988-01-28 EP EP92122046A patent/EP0550899B1/fr not_active Expired - Lifetime
- 1988-01-28 AT AT92122046T patent/ATE131153T1/de not_active IP Right Cessation
- 1988-01-29 CA CA000557711A patent/CA1339917C/fr not_active Expired - Fee Related
- 1988-02-02 ZA ZA880733A patent/ZA88733B/xx unknown
- 1988-02-04 PT PT86700A patent/PT86700B/pt not_active IP Right Cessation
- 1988-02-04 JP JP63026417A patent/JPH075534B2/ja not_active Expired - Fee Related
- 1988-02-04 IE IE30088A patent/IE63369B1/en not_active IP Right Cessation
-
1991
- 1991-01-04 US US07/637,583 patent/US5130474A/en not_active Expired - Lifetime
-
1993
- 1993-10-04 US US08/131,573 patent/US5391574A/en not_active Expired - Lifetime
-
1994
- 1994-12-01 US US08/352,818 patent/US5602179A/en not_active Expired - Lifetime
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE2049332A1 (de) * | 1969-10-13 | 1971-04-22 | Rotta Research Laboratorium SpA, Mailand (Italien) | Verfahren zur Herstellung von therapeu tisch aktiven Amiden der N Benzoylglutamm saure |
GB2160869A (en) * | 1984-06-25 | 1986-01-02 | Rotta Research Lab | Glutamic and aspartic acid derivatives |
WO1987003869A2 (fr) * | 1985-12-17 | 1987-07-02 | Rotta Research Laboratorium S.P.A | Dervies pharmaceutiquement actifs d'acides glutamiques et aspartiques |
Cited By (30)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4971978A (en) * | 1987-09-21 | 1990-11-20 | Nadzan Alex M | Derivatives of D-glutamic acid and D-aspartic acid |
GR900100516A (en) * | 1989-07-07 | 1991-12-10 | Abbott Lab | Cck analogous amino-acid antagonists |
EP0480969A1 (fr) * | 1989-07-07 | 1992-04-22 | Abbott Laboratories | Antagonistes cck analogues d'acides amines |
EP0480969A4 (en) * | 1989-07-07 | 1993-01-07 | Abbott Laboratories | Amino acid analog cck antagonists |
US5847125A (en) * | 1992-01-09 | 1998-12-08 | James Black Foundation Limited | Amino acid derivatives with anticholecystokinin activity |
WO1993014066A1 (fr) * | 1992-01-09 | 1993-07-22 | James Black Foundation Limited | Derives d'acides amines avec une activite anticholecystokinine |
US5716958A (en) * | 1994-10-27 | 1998-02-10 | Tobishi Pharmaceutical Co., Ltd. | Amino acid derivative having anti-CCK activity |
EP2246360A1 (fr) | 2003-01-28 | 2010-11-03 | Ironwood Pharmaceuticals, Inc. | Compositions pour le traitement de troubles gastrointestinaux |
EP2088154A1 (fr) | 2004-03-09 | 2009-08-12 | Ironwood Pharmaceuticals, Inc. | Procédés et compositions pour le traitement de troubles gastro-intestinaux |
EP2998314A1 (fr) | 2007-06-04 | 2016-03-23 | Synergy Pharmaceuticals Inc. | Agonistes de guanylase cyclase utiles pour le traitement de troubles gastro-intestinaux, d'inflammation, de cancer et d'autres troubles |
EP2810951A2 (fr) | 2008-06-04 | 2014-12-10 | Synergy Pharmaceuticals Inc. | Agonistes de guanylate cyclase utile dans le traitement de troubles gastro-intestinaux, d'une inflammation, d'un cancer et d'autres troubles |
EP3241839A1 (fr) | 2008-07-16 | 2017-11-08 | Synergy Pharmaceuticals Inc. | Agonistes de guanylate cyclase utiles pour le traitement de troubles gastro-intestinaux, inflammatoires, cancéreux et autres |
WO2010065751A2 (fr) | 2008-12-03 | 2010-06-10 | Synergy Pharmaceuticals, Inc. | Formulations d'agonistes de guanylate cyclase c et méthode d'utilisation |
EP3351248A1 (fr) | 2008-12-31 | 2018-07-25 | Ardelyx, Inc. | Composés et procédés d'inhibition d'un antiport à médiation par nhe dans le traitement de troubles associés à une rétention de fluide ou à une surcharge de sel et de troubles du tractus gastro-intestinal |
EP3939964A1 (fr) | 2008-12-31 | 2022-01-19 | Ardelyx, Inc. | Combinaisons d'inhibition d'un antiport a mediation par nhe dans le traitement de troubles associes a une retention de fluide ou a une surcharge de sel et de troubles du tractus gastro-intestinal |
WO2011069038A2 (fr) | 2009-12-03 | 2011-06-09 | Synergy Pharmaceuticals, Inc. | Agonistes de la guanylate cyclase utiles dans le traitement de l'hypercholestérolémie, de l'athérosclérose, d'une coronaropathie, des calculs biliaires, de l'obésité et d'autres maladies cardiovasculaires |
EP2923706A1 (fr) | 2009-12-03 | 2015-09-30 | Synergy Pharmaceuticals Inc. | Agonistes de guanylate cyclase utiles pour le traitement de l'hypercholestérolémie |
WO2012118972A2 (fr) | 2011-03-01 | 2012-09-07 | Synegy Pharmaceuticals Inc. | Procédé de préparation d'agonistes du guanylate cyclase c |
EP4309673A2 (fr) | 2012-03-15 | 2024-01-24 | Bausch Health Ireland Limited | Formulations d'agonistes de guanylate cyclase c et leurs procédés d'utilisation |
WO2013138352A1 (fr) | 2012-03-15 | 2013-09-19 | Synergy Pharmaceuticals Inc. | Formulations d'agonistes de la guanylate cyclase c et procédés d'utilisation |
EP3708179A1 (fr) | 2012-03-15 | 2020-09-16 | Bausch Health Ireland Limited | Formulations d'agonistes de guanylate cyclase c et leurs procédés d'utilisation |
WO2014029983A1 (fr) | 2012-08-21 | 2014-02-27 | Ardelyx, Inc. | Composés et procédés d'inhibition d'un antiport à médiation par nhe dans le traitement de troubles associés à une rétention de fluide ou à une surcharge de sel et de troubles du tractus gastro-intestinal |
WO2014151206A1 (fr) | 2013-03-15 | 2014-09-25 | Synergy Pharmaceuticals Inc. | Agonistes de la guanylate cyclase et leurs utilisations |
WO2014151200A2 (fr) | 2013-03-15 | 2014-09-25 | Synergy Pharmaceuticals Inc. | Compositions utiles pour le traitement de troubles gastro-intestinaux |
WO2014197720A2 (fr) | 2013-06-05 | 2014-12-11 | Synergy Pharmaceuticals, Inc. | Agonistes ultra-purs de guanylate cyclase c, leur procédé de production et d'utilisation |
WO2018129552A1 (fr) | 2017-01-09 | 2018-07-12 | Ardelyx, Inc. | Composés utiles pour le traitement de troubles du tractus digestif |
WO2018129556A1 (fr) | 2017-01-09 | 2018-07-12 | Ardelyx, Inc. | Composés et procédés pour l'inhibition d'un antiport à médiation par échangeur sodium/proton (nhe) dans le traitement de troubles associés à une rétention d'eau ou à une surcharge en sel et de troubles du tractus gastro-intestinal |
WO2018129557A1 (fr) | 2017-01-09 | 2018-07-12 | Ardelyx, Inc. | Inhibiteurs d'antiport à médiation par nhe |
CN108912007A (zh) * | 2018-06-20 | 2018-11-30 | 中国农业科学院兰州畜牧与兽药研究所 | 一种右氯谷胺的制备方法 |
CN108912007B (zh) * | 2018-06-20 | 2021-02-26 | 中国农业科学院兰州畜牧与兽药研究所 | 一种右氯谷胺的制备方法 |
Also Published As
Publication number | Publication date |
---|---|
PT86700A (pt) | 1988-03-01 |
IE63369B1 (en) | 1995-04-19 |
IT8767076A0 (it) | 1987-02-05 |
US5602179A (en) | 1997-02-11 |
DE3854764D1 (de) | 1996-01-18 |
AU1228288A (en) | 1988-08-24 |
EP0344184B1 (fr) | 1993-11-24 |
AU606390B2 (en) | 1991-02-07 |
IE880300L (en) | 1988-08-05 |
US5391574A (en) | 1995-02-21 |
JPH075534B2 (ja) | 1995-01-25 |
ZA88733B (en) | 1988-08-04 |
DE3854764T2 (de) | 1996-05-09 |
EP0344184A1 (fr) | 1989-12-06 |
EP0550899B1 (fr) | 1995-12-06 |
IT1217123B (it) | 1990-03-14 |
US5130474A (en) | 1992-07-14 |
CA1339917C (fr) | 1998-06-16 |
PT86700B (pt) | 1992-04-30 |
EP0550899A1 (fr) | 1993-07-14 |
DE3885889T2 (de) | 1994-04-07 |
JPS63201156A (ja) | 1988-08-19 |
DE3885889D1 (en) | 1994-01-05 |
ATE131153T1 (de) | 1995-12-15 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US5130474A (en) | Optically-active derivatives of (r) 5-pentylamino-5-oxopentanoic acid with antagonistic activity towards cholecystokin in and a method for their preparation | |
IE49701B1 (en) | Amides of acyl-carnitines,process for preparing same and pharmaceutical compositions containing such amides | |
KR20000053251A (ko) | 항혈전성유기질산염 | |
CA1101846A (fr) | Derives de 4-hydroxy-phenylglycine | |
EP0272228B1 (fr) | Dérivés des acides 5-pentylamino-5-oxopentanoique et 4-pentylamino-4-oxobutanoique avec une activité antagoniste envers la cholecytokinine et procédé pour leur préparation | |
JPH0784424B2 (ja) | チロシン誘導体及びその用途 | |
EP0286643B1 (fr) | Derives pharmaceutiquement actifs d'acides glutamiques et aspartiques | |
WO1992004369A1 (fr) | Derives d'acide aminosalicylique-5 destines au traitement des affections intestinales inflammatoires chroniques | |
EP0498830B1 (fr) | Derives d'acide glutamique et d'acide aspartique possedant une activite antigastrinique, et leur procede de preparation | |
EP0337774A2 (fr) | Antagonistes de CCK | |
EP0309261B1 (fr) | Amides d'acide buténoique, leur sels, compositions pharmaceutiques les contenant et leur procédé de préparation | |
US4148912A (en) | Pharmaceutical compositions and methods of using the same | |
DK172007B1 (da) | Farmaceutisk aktive derivater af (R)-5-pentyl-amino-5-oxopentansyre og farmaceutisk præparater deraf | |
JPH0473425B2 (fr) | ||
KR19990007000A (ko) | 아미드 유도체 | |
IE51324B1 (en) | Esters of substituted benzoic acid |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AK | Designated states |
Kind code of ref document: A1 Designated state(s): AU DK |
|
AL | Designated countries for regional patents |
Kind code of ref document: A1 Designated state(s): AT BE CH DE FR GB IT LU NL SE |
|
WWE | Wipo information: entry into national phase |
Ref document number: 1988901259 Country of ref document: EP |
|
WWP | Wipo information: published in national office |
Ref document number: 1988901259 Country of ref document: EP |
|
WWG | Wipo information: grant in national office |
Ref document number: 1988901259 Country of ref document: EP |